The long-term objective of this program is to obtain better quantitative assessment of the hazard to human health posed by the presence of heavy metals in our environment. The projects constitute a broad program ranging from studies of dose-response relationships in exposed populations and the pharmacokinetics of tracer doses of metals in volunteers to observations on the effects of metals at cellular and subcellular levels. The projects have been arranged in five main sections. The first section describes studies of dose-response relationships in populations differing in intensity and duration of exposure to methylmercury. These populations will also be used to test the current metabolic model for methylmercury in man. The second and third sections describe studies of the dose-effect relationships in laboratory animals exposed to mercurial compounds. Their main purpose is to attain a better understanding of the actions of methylmercury on the nervous system and to develop more sensitive tests for adverse effects of methylmercury in man. Such tests may bring to light critical effects as yet unknown; of special interest in this respect is the project on detection of somatic cell point mutations in humans, making use of amino acid substitutions in hemoglobin. Section four is devoted to obtaining precise quantitative information on the relationships of exposures to doses, through studies of the kinetic of heavy metals in man. These include projects on dietary absorption of mercury, cadmium, and lead and on inhalation of lead aerosols. Section five is concerned with reproductive and developmental toxicology. These projects include observations on metal transfer from mother to fetus and from mother to infant via milk, and on the biological effects of metals during the processes of reproduction and development. Their prime objective is the determination of critical effects on developing brains and gonads.